The expression level of miR-18b in hepatocellular carcinoma is associated with the grade of malignancy and prognosis

Murakami, Yoshiki; Tamori, Akihiro; Itami, Saori; Tanahashi, Takao; Toyoda, Hidenori; Tanaka, Masami; Wu, Wei; Brojigin, Nariso; Kikuchi, Yuji; Maeda, Atsuyuki; Kumada, Takashi; Kawada, Norifumi; Kubo, Shoji; Kuroda, Masahiko

doi:10.1186/1471-2407-13-99

Cited by 66 publications

(61 citation statements)

References 27 publications

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“…miR-18b plays an oncogenic or tumor suppressive role in different cancer types (17). For instance, miR-18b is upregulated in HCC, and higher miR-18b level predicates poor prognosis (18). Moreover, overexpression of miR-18b increased HCC cell proliferation, while inhibited cell adhesion ability, indicating that miR-18b acts as an oncogene in HCC (18).…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-18b inhibits the growth of malignant melanoma via inhibition of HIF-1α-mediated glycolysis

et al. 2016

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Abstract. MicroRNAs (miRs) have been demonstrated to play critical roles in the development and progression of malignant melanoma (MM). However, the exact role and underlying mechanism of miR-18b in MM growth remains unclear. In the present study, real-time PCR data indicated that miR-18b was significantly downregulated in MM tissues compared to their matched adjacent non-tumor tissues. Low miR-18b expression was significantly associated with the tumor thickness and stage, although no significant association was observed between the miR-18b expression and the age, gender, or lymph node metastasis. Besides, miR-18b was also significantly downregulated in MM B16 and A375 cells compared to normal skin HACAT cells. Ectopic expression of miR-18b decreased the proliferation of A375 and B16 cells, while induced a remarkable cell cycle arrest at G1 stage. Besides, miR-18b overexpression also inhibited the glycolysis in A375 and B16 cells. HIF-1α, a key regulator in glycolysis, was then identified as a target gene of miR-18b, and its expression was negatively mediated by miR-18b in A375 and B16 cells. Overexpression of HIF-1α rescued the suppressive effect of miR-18b on MM cell proliferation and glycolysis. In vivo study further showed that overexpression of miR-18b inhibited the MM growth as well as the tumor-related death, accompanied with HIF-1α downregulation. Taken together, the present study suggests that miR-18b inhibits the growth of MM cells in vitro and in vivo through directly targeting HIF-1α.

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Section: Introductionmentioning

confidence: 99%

“…For instance, miR-18b is upregulated in HCC, and higher miR-18b level predicates poor prognosis (18). Moreover, overexpression of miR-18b increased HCC cell proliferation, while inhibited cell adhesion ability, indicating that miR-18b acts as an oncogene in HCC (18). On the contrary, miR-18b was recently reported to inhibit MM (19).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-18b inhibits the growth of malignant melanoma via inhibition of HIF-1α-mediated glycolysis

et al. 2016

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“…A number of miRNAs have been revealed to be involved in the pathogenesis of HCC (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). The roles of miR-1271 in numerous types of cancers have previously been investigated.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑1271 inhibits cellular proliferation of hepatocellular carcinoma

et al. 2017

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Abstract. Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-associated mortality worldwide, particularly in China. MicroRNAs (miRs) serve important roles in the pathogenesis of HCC. The present study investigated the function of miR-1271 in HCC. The miR-1271 levels were analyzed by quantitative reverse transcription polymerase chain reaction. Cells growth was examined by MTT assay. Bioinformatics algorithms from TargetScanHuman were used to predict the target genes of miR-1271. The protein level was assayed by western blotting. miR-1271 demonstrated a lower expression level in HCC tissues. Upregulation of miR-1271 suppressed the growth of HepG-2 and Huh-7 cells and induced apoptosis of cells. Forkhead box Q1 (FOXQ1) was targeted by miR-1271. In conclusion, miR-1271 is a novel tumor suppressor that inhibits HCC proliferation and induces cellular apoptosis by targeting FOXQ1 in HCC. The results of the present study may provide a novel therapeutic target of HCC. IntroductionHepatocellular carcinoma (HCC) accounts for ~80% of all liver cancer cases, and is one of the most common causes of cancer-associated mortality worldwide (1,2). The prevalence rate of HCC in China is particularly high, but continues to increase in numerous western countries (1,3). Despite HCC being was one of the first cancers to be linked epidemiologically to a definite risk factor, the underlying mechanisms of HCC pathogenesis remain unclear (4). The risk factors for HCC vary by location. In China, Hepatitis B or Hepatitis C virus infections are the main risk factors (5). The survival rate of patients with HCC has been extended due to progress in liver transplantation and other treatments; however, the insensitivity of chemotherapeutic drugs, cancer recurrence and metastasis continue to contribute to a poor prognosis (6). Thus, the identification of therapeutic targets and translation of molecular studies of HCC into clinical practice is urgently required.MicroRNAs (miRNAs) are a class of small non-coding RNAs, which are ~22 nucleotides in length (7-9). A number of miRNAs have been revealed to be involved in the pathogenesis of HCC (10-26). The roles of miR-1271 in numerous types of cancers have previously been investigated. For example, in gastric cancer, miR-1271 inhibited cell proliferation, invasion and epithelial-mesenchymal transition (EMT) by targeting forkhead box Q1 (FOXQ1) (27). Additionally, in oral squamous cell carcinoma, miR-1271 inhibited cell growth and metastasis by targeting anaplastic lymphoma receptor tyrosine kinase (28). In HCC, a previous study demonstrated that miR-96, miR-129-1-3p, miR-1291, miR-1303 and miR-1271 differentially regulated Glypican-3 (GPC3) expression levels in HCC cells and that the upregulation of GPC3 was associated with a concomitant downregulation of its repressor miR-1271 (29). However, the roles served by miR-1271 in HCC remain unclear.The present study analyzed the expression level of miR-1271 in HCC tissues and determined the in vitro function of miR-1271. The aim of the ...

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“…miRNA-18b was highly expressed in breast cancer and modulated gene expression levels involved in cell migration (22). The expression level of miR-18b in hepatocellular carcinoma was associated with the grade of malignancy and prognosis (26). The results of the present study have revealed that miR-18b was significantly upregulated and promoted human OC cell migration and invasion.…”

Section: Discussionmentioning

confidence: 54%

“…Previous studies have demonstrated that the aberrant expression level of miR-18b may be present in diverse human pathologies, including multiple sclerosis, cardiac hypertrophy and chronic hepatitis B virus infection (22,23). miR-18b has attracted much attention as it is frequently upregulated and acts as a oncogene in human gastric cancer (24), colonic cancer (25), breast cancer (22) and hepatocellular carcinoma (26). However, whether miR-18b is involved in the development and progression of OC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of microRNA‑18b induces phosphatase and tensin homolog to accelerate the migration and invasion abilities of ovarian cancer

et al. 2017

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Abstract. Ovarian cancer (OC) is the most common cause of mortality from malignant gynecological cancers. Its lethality is mainly a result of tumors that are difficult to detect at the early stage and a lack of effective systemic therapy for advanced status cancer. MicroRNAs (miRNAs/miRs) are a category of single-stranded non-coding small RNAs that bind to their target mRNAs, and aberrant expression levels of miRNAs may serve key roles in regulating cell migration and invasion of various types of human cancer. Previous studies have demonstrated that miR-18b may function as an oncogene in numerous types of tumors, but its role and molecular mechanism in OC remained unclear. The present study demonstrated for the first time that miR-18b expression was significantly upregulated in OC tissues and cells. An increased miR-18b expression level was positively associated with tumor grade and lymph node metastasis. An in vitro assay revealed that exogenous inhibition of miR-18b expression may markedly inhibit OC cell migratory and invasive activities, whereas overexpression of miR-18b enhanced cell migratory and invasive abilities. Of note, using in silico methodologies and luciferase reporter assays, it was demonstrated that phosphatase and tensin homolog (PTEN) was a direct target of miR-18b in OC cells. Furthermore, knockdown of miR-18b expression may significantly decrease mRNA and protein expression levels of endogenous PTEN. The results of the present study highlighted that upregulation of miR-18b was involved in OC cell metastasis by directly targeting PTEN. Inhibition of miR-18b may be a novel effective diagnostic and therapeutic measure for OC.

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The expression level of miR-18b in hepatocellular carcinoma is associated with the grade of malignancy and prognosis

Cited by 66 publications

References 27 publications

MicroRNA-18b inhibits the growth of malignant melanoma via inhibition of HIF-1α-mediated glycolysis

MicroRNA-18b inhibits the growth of malignant melanoma via inhibition of HIF-1α-mediated glycolysis

MicroRNA‑1271 inhibits cellular proliferation of hepatocellular carcinoma

Upregulation of microRNA‑18b induces phosphatase and tensin homolog to accelerate the migration and invasion abilities of ovarian cancer

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